Aqueous 6emsp14;+emsp14;4 cycloadditions of tropone with 1-(glucopyranosyloxy)buta-1,3-diene

摘要

J. Chem. Soc. Perkin Trans. 1 1997 2863 Aqueous 6 1 4 cycloadditions of tropone with 1-(glucopyranosyloxy) buta-1,3-diene Andreacute; Lubineau a Giliane Bouchain a and Yves Queneau a,b a Laboratoire de Chimie Organique Multifonctionnelle CNRS URA 462 Institut de Chimie Moleacute;culaire drsquo;Orsay Universiteacute; de Paris-Sud Bat. 420 91405 Orsay Cedex France b Present address Uniteacute; Mixte de Sucrochimie CNRS-Beacute;ghin-Say (UMR 143) c/o Eridania Beacute;ghin-Say CEI 27 Bd du 11 novembre 1918 BP 2132 69603 Villeurbanne Cedex France The first aqueous 6 1 4 cycloaddition reaction is reported. Starting from tropone and glucopyranosyloxybuta- 1,3-diene bicyclic adducts arising from the expected exo-transition state have been obtained in fair yields under much milder conditions than those usually required thus preventing side-4 1 2 adduct formation by limiting the reversibility of the 6 1 4 process.Influence of the solvent is clearly demonstrated as the reaction in methanol is much slower compared with that in water. The best yields are obtained in buffered solutions or in concentrated aq. sugar solutions. Introduction The 6 1 4 cycloaddition reaction of tropone with dienes allows the construction of the bicyclo4.4.1undecanone backbone which can serve as the starting point for the synthesis of complex polycyclic compounds such as troponophanes cyclodecenes and some diterpenes in the ingenol series.1 This reaction was first reported in the mid 60s in the case of cyclopentadiene which provided exo-oriented adducts 2 as predicted by the Woodwardndash;Hoffmann rules.3 The condensation of non-substituted tropone with simple dienes is not an easy process as confirmed by the high temperature and long reaction time which are often necessary.4 Owing to the greater reversibility of the 6 1 4 cycloaddition pathway compared with the 4 1 2 one 4 1 2 adducts can be the major products upon prolongation of the reaction time.5 It is therefore useful to investigate new conditions for such reactions.A possibility is to catalyse the reaction using transition metal catalysts.6 Based on our experience in cycloadditions using water as the solvent,7 we studied the outcome of the reaction of tropone in aqueous medium using the water-soluble 1-(b-D-glucopyranosyloxy)- buta-1,3-diene 1.8 Indeed we showed that in water such a diene could provide 4 1 2 cycloaddition adducts with both rate and selectivity increase compared with other solvents.9 Widening the scope of the use of this diene in aqueous medium we report herein the synthesis of 2-(glucopyranosyloxy)- bicyclo4.4.1undecanones as the first 6 1 4 cycloaddition reaction performed in water.Results and discussion Cycloaddition of b-D-glucopyranosyloxybuta-1,3-diene 1 with cyclohepta-2,4,6-trienone (tropone) 3 was performed in aqueous medium to provide adducts 4ab as a mixture of two diastereoisomers in nearly equivalent amounts (Scheme 1) which were characterized as their per-acetylated derivatives 5ab. The relative stereochemistry in adducts 4ab was assigned by comparison with known derivatives after reduction and hydrolysis (vide infra). Reaction conditions and yields are given in Table 1. The necessity of keeping the temperature below 60 8C to prevent substantial hydrolysis of the starting diene led to quite long reaction times.This had a positive consequence for the 6 1 4 process whose reversibility was inhibited therefore preventing side-4 1 2 cycloadditions to occur. Nevertheless moderate to fair yields of adducts 4ab could be obtained at 40 or 50 8C which is an exceptionally low temperature for a 6 1 4 cycloaddition. For example a temperature of 80 8C is necessary for reaction of cyclopentadiene,2a although a much more reactive diene and refluxing xylene during 5 days is necessary for the cycloaddition with 1-acetoxybuta-1,3-diene.4a The reaction Scheme 1 Reagents and yields i see Table 1; ii Ac2O Py (96); iii 3 water (66); iv Ac2O Py (92). Arbitrary NMR numbering scheme is shown for structures 4 and 5.O + O RO RO OR OR O 3 O RO RO OR OR O H O 13 14 15 16 7 12 11 10 9 8 O RO RO OR OR O H O + i 4ab R = H 5ab R = Ac ii O HO HO OH OH O iii O RO RO OR OR O H O O RO RO OR OR O H O 7ab R = H 8ab R = Ac iv + 1 R = H 2 R = Ac 6 2864 J. Chem. Soc. Perkin Trans. 1 1997 Table 1 Reaction conditions and yields for adducts 4ab and 7ab (Scheme 1) Entry 1 2 3 4 5 6 7 8 9 10 Diene (mol equiv.) 1 (0.5) 1 (0.5) 2 (0.5) 1 (0.5) 1 (0.5) 1 (2.0) 1 (1.8) 1 (0.5) 1 (0.5) 6 (1.8) Solvent water methanol toluene water pH 7 buffer pH 7 buffer pH 7 buffer 1 hydroquinone 4 M glucose 2.5 M sucrose pH 7 buffer 1 hydroquinone T/8C 40 40 110 50 50 50 50 40 40 50 t/days 9.5 12 10 3.5 6.5 6.5 6.5 9.5 9.5 6.5 Yield () 45 28 44 46 54 58 62 62 59 66 of diene 1 with tropone 3 was shown to be very sensitive to the nature of the solvent as a much lower yield was obtained in methanol (entry 2) and a much slower reaction was observed for the acetylated diene 2 in toluene (entry 3).Yields could be improved by conducting the reaction in water at 50 8C in the presence of additives (entries 5ndash;7) such as (i) pH 7 phosphate buffer in order to prevent competitive hydrolysis of diene and (ii) hydroquinone to inhibit polymerization of diene. Concentrated glucose and sucrose as aqueous solutions were also used (entries 8 and 9) for which yields of ~60 were obtained. We have already described the use of such a solvent mixture for Dielsndash;Alder reactions and other transformations.10 It was shown that the rate increase was due to enforced hydrophobic effects. The a-glucosyl diene 6 was also shown to provide similar adducts 7ab which were characterized as their per-acetylated derivatives 8ab.In order to establish the stereochemistry (exo) of the glycosylated bicyclo4.4.1undecanones compounds 4ab were submitted to hydrolysis. As alcohol 13 has already been described in the literature,4a adducts 4ab were hydrogenated under classical conditions (10 Pd/C 14 psi H2) to provide compounds 9ab which were characterized as their benzoylated derivatives 10ab (Scheme 2). It is to be noted that at this stage the two diastereoisomers 9ab could be separated by flash chromatography but attempts to establish the absolute configuration at the newly created chiral centres were unsuccessful. The same synthetic sequence was applied to the a-anomers 7ab allowing isolation of hydrogenated glycosides 11ab and their benzoylated derivatives 12ab.Acidic hydrolysis (0.5 M H2SO4; 100 8C) of glycosides 9ab albeit in moderate yield (47) allowed us to identify keto alcohol 13 (by comparison with literature NMR data) as the sole product thus confirming the total exo selectivity of the cycloaddition. Similar treatment of each of the two compounds 9a and 9b as pure isomers allowed us to obtain (1)-13 and (2)-13 for which an aD value of 19 and 29 were measured. Hydrogenated adducts in the a series 7ab could be hydrolysed to provide 13 in similar yield (42). Direct hydrolysis of adducts without previous hydrogenation of the three double bonds appeared to be a much more complicated process. Indeed intermediate keto alcohols (such as that having structure 14) could not be isolated before subsequent oxy-Cope3,3 sigmatropic rearrangement as shown by isolation of structures 15ab (31) after acidic treatment (0.5 M H2SO4; 80 8C) together with hemiacetals 16ab (13) arising from hydration of one of compounds 15ab having a cis relationship between the oxoethyl chain and the enone bridge.Their structures were determined by 1H COSY NMR analysis. A similar oxycope rearrangement has already been described in the literature.5b Conclusions In this paper we have reported the first aqueous 6 1 4 cycloaddition of tropone using water-soluble dienes derived from carbohydrates. The reaction was shown to proceed at much lower temperature compared with the usual conditions providing fair yields of glycosylated bicyclo4.4.1undecanones. The exo selectivity was confirmed after hydrogenation and hydrolysis and pure enantiomers of 7-hydroxybicyclo4.4.1- undecanone 13 could be isolated.Experimental General NMR spectra were recorded with Bruker AC200 and 250 spectrometers. d-Values are given in ppm downfield from internal Scheme 2 Reagents and yields i H2 Pd/C MeOH (98); ii BzCl Py; iii H2 Pd/C MeOH (97); iv 0.5 M H2SO4 O RO RO OR OR O H O RO RO OR OR O H O O RO RO OR OR O H O 4ab O RO RO OR OR O H O 13 14 15 16 7 12 11 10 9 8 9ab R = H 10ab R = Bz ii + i 7ab iii + 11ab R = H 12ab R = Bz ii O H HO 9ab iv O H HO (plusmn;)-13 14 O CHO H O H CHO H O O OH 17 8 9 12 11 10 15 16 7 14 14 17 8 9 12 11 10 15 16 7 13 13 15ab 16ab + J. Chem. Soc. Perkin Trans. 1 1997 2865 tetramethylsilane and J-values are given in Hz. Carbohydrate entities are described with the classical numbering.Position 7 is arbitrarily assigned to the bicyclic ringrsquo;s carbon linked to oxygen. Positions 8 and 13 are assigned to the ring junction. IR spectra were recorded using a Bruker FT instrument. Flash chromatography was performed using 6ndash;35 mm silica gel (60) purchased from S.D.S. TLC was performed using Merck 60 F254 plates and visualized first with UV light and then by heating after treatment with alcoholic sulfuric acid. Elementary analyses were performed at the Service Central de Microanalyse du C.N.R.S. Optical rotations were measured on a JASCO (DIP- 370) spectrometer with aD-values given in units of 1021 deg cm2 g21. (1R*,6R*,7R*)-7-(lsquor;-D-Glucopyranosyloxy)bicyclo4.4.1- undeca-2,4,8-trien-11-one 4ab b-D-Glucopyranosyloxybuta-1,3-diene 1 8 (1.89 g 8.1 mmol) tropone 3 (1.42 cm3 14.65 mmol) and hydroquinone (10 mg 0.09 mmol) were heated in phosphate buffer (1 M pH 7; 16.2 cm3) at 50 8C for 6 days.After being cooled to room temperature the mixture was diluted with water (3 cm3) and extracted with dichloromethane (2 times; 3 cm3). The aqueous layer was concentrated under reduced pressure. The residue was purified by flash chromatography (CH2Cl2ndash;MeOH 94 6) to give compounds 4ab (1.7 g 62) as a syrup (Found C 58.1; H 6.7. C17H22O7?0.66H2O requires C 58.3; H 6.7). Isomer 4a dH(250 MHz; D2O) 2.52ndash;2.74 (2 m 2 H 14-H2) 3.22ndash;4.0 (m 8 H 2- 3- 4- 5- 8- and 13-H and 6-H2) 4.52 (d J 8 1 H 1-H) 4.94ndash;5.05 (m 1 H 7-H) 5.69ndash;6.02 (m 4 H 9- 12- 15- and 16-H) and 6.12ndash;6.36 (m 2 H 10- and 11-H); dC(62 MHz; D2O) 29.23 (C-14) 54.94 (C-13) 60.64 (C-6) 62.47 (C-8) 69.58 72.95 74.18 75.74 75.87 (C-2 -3 -4 -5 and -7) 100.96 (C-1) 124.25 125.71 127.53 130.22 130.38 and 131.41 (C-9 -10 -11 -12 -15 and -16) and 209.73 (CO).Isomer 4b dH(250 MHz; D2O) 2.56ndash;2.67 (2 m 2 H 14-H2) 3.15ndash;3.97 (m 8 H 2- 3- 4- 5- 8- and 13-H and 6-H2) 4.61 (d J 8 1 H 1-H) 4.95ndash;5.09 (m 1 H 7-H) 5.74ndash;5.90 (m 4 H 9- 12- 15- and 16-H) and 6.18ndash;6.36 (m 2 H 10- and 11-H); dC(62 MHz; D2O) 29.25 (C-14) 54.76 (C-13) 60.59 (C-6) 61.62 (C-8) 69.53 73.18 75.50 and 76.0 (C-2 -3 -4 -5 and -7) 102.28 (C-1) 124.95 126.53 128.14 129.65 130.65 and 132.21 (C-9 -10 -11 -12 -15 and -16) and 208.17 (CO). (1R*,6R*,7R*)-7-(2,3,4,6-Tetra-O-acetyl-lsquor;-D-glucopyranosyloxy) bicyclo4.4.1undeca-2,4,8-trien-11-one 5ab To a stirred solution of glucosylated compounds 4ab (45 mg 0.13 mmol) in pyridine (0.16 cm3) cooled to 0 8C and under nitrogen was added acetic anhydride (0.11 cm3 1.22 mmol).The reaction mixture was stirred for 12 h before removal of the solvent under reduced pressure to leave a crude product as a yellow oil. This oil was recrystallized in diethyl ether to give compounds 5ab (63 mg 96) as a solid (Found C 59.0; H 6.1. C25H30O11 requires C 59.3; H 6.0). The two diastereoisomers have been partially separated then deacetylated to give tetraols 4a and 4b. Isomer 5a (Found C 58.8; H 6.1); mp 116ndash;117 8C; nmax(neat)/cm21 3022 1758 1709 1522 1427 1368 1215 1041 and 929; aD 27 14 (c 0.45 CH2Cl2); dH(250 MHz; CDCl3) 2.0 2.01 and 2.10 (4 s 12 H CH3) 2.35ndash;2.52 (m 1 H 14-H) 2.59ndash;2.75 (m 1 H 14-H9) 3.40ndash;3.50 (m 1 H 13-H) 3.59ndash;3.69 (m 1 H 5-H) 3.70ndash;3.79 (dt J 1 and 8 1 H 8-H) 4.15 (dd J 2 and 12 1 H 6-H) 4.20 (dd J 5 and 12 1 H 6-H9) 4.51 (d J 8 1 H 1-H) 4.72ndash;4.82 (m 1 H 7-H) 4.91ndash;5.23 (m 3 H 2- 3- and 4-H) 5.49ndash;5.60 and 5.61ndash;5.86 (2 m 4 H 9- 12- 15- and 16-H) and 6.01ndash;6.13 (m 2 H 10- and 11-H); dC(62 MHz; CDCl3) 20.56 and 20.69 (4 times; CH3) 31.30 (C-14) 54.49 (C-13) 60.07 (C-6) 62.96 (C-8) 68.46 71.26 71.79 and 72.73 (C-2 -3 -4 and -5) 74.39 (C-7) 99.12 (C-1) 125.68 125.77 126.88 130.07 131.30 and 132.20 (C-9 -10 -11 -12 -15 and -16) 169.03 169.32 170.27 and 170.51 (CO2) and 203.21 (CO).Isomer 5b (Found C 59.0; H 5.95); aD 28 229 (c 0.7 CH2Cl2); mp 166ndash;167 8C; nmax(neat)/cm21 3022 1757 1711 1522 1424 1366 1215 1040 and 929; dH(250 MHz; CDCl3) 2.0 2.04 and 2.10 (4 s 12 H CH3) 2.37ndash;2.52 (m 1 H 14-H) 2.58ndash; 2.75 (m 1 H 14-H9) 3.43ndash;3.54 (m 1 H 13-H) 3.58ndash;3.72 (2 m 2 H 5- and 8-H) 4.12 (dd 1 H J 2 and 12 6-H) 4.26 (dd 1 H J 5 and 12 6-H9) 4.59 (d J 8 1 H 1-H) 4.73ndash;4.84 (m 1 H 7-H) 4.97 (dt J 8 and 10 1 H 2-H) 5.08 (t 1 H J 10 4-H) 5.20 (t 1 H J 10 3-H) 5.55ndash;5.78 and 5.80ndash;5.92 (2 m 4 H 9- 12- 15- and 16-H) and 6.03ndash;6.19 (m 2 H 10- and 11-H); dC(62 MHz; CDCl3) 20.59 20.61 20.71 and 20.74 (CH3) 30.98 (C-14) 54.55 (C-13) 61.87 (C-6) 62.27 (C-8) 68.34 71.18 71.74 and 72.62 (C-2 -3 -4 and -5) 75.65 (C-7) 100.62 (C-1) 125.71 127.60 128.22 132.15 and 133.32 (C-9 -10 -11 -12 -15 and -16) 169.27 169.39 170.30 and 170.65 (CO2) and 202.58 (CO).Starting from the acetylated diene 27b (20 mg 0.05 mmol) as a solution in toluene (0.1 cm3) with tropone (0.01 cm3 0.1 mmol) the reaction mixture was heated at reflux for 10 days.Removal of the solvent followed by flash chromatography (hexanendash;ethyl acetate 7 3) yielded adducts 5ab (11 mg 44). (1R*,6R*,7R*)-7-(2,3,4,6-Tetra-O-acetyl-middot;-D-glucopyranosyloxy) bicyclo4.4.1undeca-2,4,8-trien-11-one 8ab The same procedure described for anomers 4ab was used starting from a-D-glucopyranosyloxybuta-1,3-diene 68 (2 g 8.6 mmol) and tropone 3 (1.5 cm3 15.8 mmol) in phosphate buffer (17.2 cm3). Compounds 7ab {7-(a-D-glucopyranosyloxy)- bicyclo4.4.1undeca-2,4,8-trien-11-one} (1.9 g 66) were obtained as a syrup (ratio 55 45) (Found C 57.5; H 6.4. C17H22O7?0.83H2O requires C 57.8; H 6.7); nmax(KBr)/cm21 3388 3031 2929 1698 1407 1338 1259 1145 1076 and 1026; dH(250 MHz; D2O) 2.57ndash;2.67 (2 m 4 H 14-H2) 3.35ndash;3.90 (m 16 H 2- 3- 4- 5- 8- and 13-H and 6-H2) 4.80ndash;4.94 (m 2 H 7-H) 4.98 (d 1 H J 4 1-H) 5.10 (m 1 H J 4 1-H) 5.63ndash;5.96 (m 8 H 9- 12- 15- and 16-H) and 6.15ndash;6.32 (m 4 H 10- and 11-H); dC(62 MHz; D2O) 29.44 and 31.17 (C-14) 53.85 and 54.83 (C-13) 60.16 and 60.35 (C-6) 61.80 and 62.30 (C-8) 69.27 69.50 70.05 71.01 71.34 72.0 72.38 72.91 and 73.36 (C-2 -3 -4 -5 and -7) 96.09 and 98.58 (C-1) 124.70 125.30 126.16 128.05 128.47 129.70 130.64 131.61 131.95 and 132.42 (C-9 -10 -11 -12 -15 and -16) and 208.81 (CO).Further acetylation using the same procedure as for anomers 5ab led starting from tetraols 7ab (1.7 g 5 mmol) to acetylated derivatives 8ab (2.33 g 92) as a powder (Found C 58.4; H 6.0. C25H30O11?0.5H2O requires C 58.3; H 6.1); nmax(KBr)/cm21 1762 1760 1753 1749 1741 1254 1246 1239 1236 1229 1225 1217 and 1046; dH(250 MHz; CDCl3) 1.99ndash; 2.18 (m 24 H CH3) 2.33ndash;2.55 (m 2 H 14-H) 2.64ndash;2.85 (m 2 H 14-H9) 3.42ndash;3.58 (m 2 H 13-H) 3.60ndash;3.68 (dt 1 H J 2 and 8 8-H) 3.70ndash;3.80 (dt J 2 and 8 1 H 8-H) 3.96ndash;4.35 (m 6 H 5-H and 6-H2) 4.68ndash;4.89 (m 2 H 7-H) 4.98ndash;5.53 (m 8 H 1- 2- 3- and 4-H) 5.53ndash;5.90 (m 8 H 9- 12- 15- and 16-H) and 6.02ndash;6.20 (m 4 H 10- and 11-H); dC(62 MHz; CDCl3) 20.63 (8 times; CH3) 30.58 and 31.32 (C-14) 54.29 and 54.81 (C-13) 61.64 (2 times; C-6) 61.98 and 62.40 (C-8) 67.48 67.70 68.27 68.49 70.03 and 70.70 (2 times; C-2 -3 -4 and -5) 72.59 and 73.86 (C-7) 94.45 and 95.62 (C-1) 125.09 125.43 125.73 127.68 129.75 131.60 132.10 and 132.55 (C-9 -10 -11 -12 -15 and -16) 169.56 169.98 and 170.53 (8 times; CO2) and 202.60 and 202.71 (CO).(1R*,2R*,6S*)-2-(2,3,4,6-Tetra-O-benzoyl-lsquor;-D-glucopyranosyloxy) bicyclo4.4.1undecan-11-one 10a and 10b A solution of adducts 4ab (250 mg 0.74 mmol) and 150 mg of 10 palladium on carbon in 5 cm3 of methanol were placed under 14 psi of hydrogen and the mixture was shaken for 24 h.The suspension was filtered through Celite and the filtrate was concentrated under reduced pressure. Separation of diastereoisomers was achieved by flash chromatography (CH2Cl2ndash; 2866 J. Chem. Soc. Perkin Trans. 1 1997 MeOH 94 6) to provide purified samples of compounds 9a and 9b {2-(b-D-glucopyranosyloxy)bicyclo4.4.1undecan-11- one} (250 mg 98) as a powder in a 55 45 ratio. Compound 9a mp 60ndash;62 8C; nmax(KBr)/cm21 3409 2927 2868 1681 1650 1445 1365 1278 1162 1076 1039 and 1010; aD 28 269 (c 1.04 CH2Cl2); dH(250 MHz; D2O) 1.15ndash;2.29 (m 14 H 9- 10- 11- 12- 14- 15- and 16-H2) 2.70ndash;2.87 (m 1 H 13-H) 2.92ndash;3.05 (m 1 H 8-H) 3.20ndash;3.57 (m 4 H 2- 3- 4- and 5-H) 3.72 (dd J 5 and 12 1 H 6-H) 3.85 (dd 1 H J 2 and 12 6-H9) 4.19ndash;4.30 (m 1 H 7-H) and 4.60 (d J 8 1 H 1-H); dC(62 MHz; D2O) 21.09 25.54 25.75 27.30 28.85 and 33.52 (C-9 -10 -11 -12 -14 -15 and -16) 54.93 (C-13) 60.12 (C-8) 60.76 (C-6) 69.65 73.41 75.62 and 75.99 (C-2 -3 -4 and -5) 78.91 (C-7) 102.65 (C-1) and 219.58 (CO).Compound 9b mp 68ndash;70 8C; nmax(KBr)/cm21 3409 2918 2867 1684 1456 1361 1186 1160 1078 and 1037; aD 26 223 (c 1 CH2Cl2); dH(250 MHz; D2O) 1.15ndash;2.30 (m 14 H 9- 10- 11- 12- 14- 15- and 16-H2) 2.70ndash;2.92 (m 2 H 13-H) 3.25 (t J 8 1 H 8-H) 3.18ndash;3.56 (m 4 H 2- 3- 4- and 5-H) 3.74 (dd J 5 and 12 1 H 6-H) 3.92 (dd J 1 and 12 1 H 6-H9) 4.32 (br t J 8 1 H 7-H) and 4.52 (d J 8 1 H 1-H); dC(62 MHz; D2O) 20.98 25.39 25.78 26.35 27.85 28.67 and 32.09 (C-9 -10 -11 -12 -14 -15 and -16) 54.79 (C-13) 60.66 (C-6) 60.96 (C-8) 69.67 72.93 75.82 and 75.92 (C-2 -3 -4 and -5) 76.31 (C-7) 100.41 (C-1) and 219.41 (CO).To a stirred solution of tetraol 9a (90 mg 0.26 mmol) in pyridine (0.53 cm3) was added benzoyl chloride (0.17 cm3 1.44 mmol). The reaction mixture was stirred for 2.5 h at room temperature under nitrogen. Benzoyl chloride in excess was quenched by 0.3 cm3 of methanol and then dichloromethane (5 cm3) and water (3 cm3) were added. The organic phase was washed successively with dil. aq. hydrochloric acid (3 cm3) and saturated aq. NaHCO3 (3 cm3) and was then dried over MgSO4. After filtration the solution was concentrated under reduced pressure to give a pale yellow syrup. Flash chromatography of the residue (toluenendash;diethyl ether 95 5) provided tetrabenzoate 10a (175 mg 88).Using the same procedure starting from the diastereoisomer 9b (96 mg 0.28 mmol) compound 10b (117 mg 56) was obtained. Compound 10a mp 87ndash;89 8C (Found C 71.1; H 5.8. C45H44O11 requires C 71.0; H 5.8); nmax(KBr)/cm21 3630 3536 3440 3063 2928 2857 1729 1692 1602 1584 1492 1452 1365 1267 1177 1111 1069 and 1027; aD 23 123 (c 1.1 CH2Cl2); dH(200 MHz; CDCl3) 0.80ndash;1.85 and 2.10ndash;2.27 (2 m 14 H 9- 10- 11- 12- 14- 15- and 16-H2) 2.50ndash;2.67 (m 1 H 13-H) 2.74ndash;2.88 (m 1 H 8-H) 4.10ndash;4.28 (m 2 H 5- and 7-H) 4.50 (dd J 6 and 12 1 H 6-H) 4.63 (dd J 3 and 12 1 H 6-H9) 5.04 (d J 8 1 H 1-H) 5.50 (dd J 8 and 10 1 H 2-H) 5.60 (t J 10 1 H 4-H) 5.93 (t J 10 1 H 3-H) and 7.14ndash;7.61 and 7.79ndash; 8.08 (2 m 20 H 4 times; Ph); dC(62 MHz; CDCl3) 21.55 25.90 26.17 26.98 27.15 30.0 34.60 (C-9 -10 -11 -12 -14 -15 and -16) 53.89 (C-13) 59.73 (C-8) 63.16 (C-6) 69.82 71.97 72.12 and 72.73 (C-2 -3 -4 and -5) 78.16 (C-7) 100.90 (C-1) 128.17 128.27 128.58 128.64 129.09 129.43 129.55 129.62 129.69 133.09 and 133.38 (4 times; Ph) 164.89 165.15 165.67 and 165.87 (CO2) and 215.82 (CO).Compound 10b mp 90ndash;92 8C (Found C 71.1; H 6.0); nmax(KBr)/cm21 3630 3550 3063 2928 2855 1736 1685 1602 1584 1492 1452 1358 1264 1177 1094 1061 and 1026; aD 27 25 (c 1.05 CH2Cl2); dH(250 MHz; CDCl3) 0.95ndash;2.17 (m 14 H 9- 10- 11- 12- 14- 15- and 16-H2) 2.55ndash;2.68 (m 1 H 13-H) 2.70ndash;2.82 (m 1 H 8-H) 4.15ndash;4.32 (m 2 H 5- and 7-H) 4.54 (dd J 6 and 12 1 H 6-H) 4.63 (dd J 3 and 12 1 H 6-H9) 4.92 (d J 8 1 H 1-H) 5.49 (dd J 8 and 10 1 H 2-H) 5.63 (t J 10 1 H 4-H) 5.93 (t J 10 1 H 3-H) and 7.01ndash;7.60 and 7.79ndash;8.09 (2 m 20 H 4 times; Ph); dC(62 MHz; CDCl3) 21.80 25.67 26.16 27.51 30.95 and 33.19 (C-9 -10 -11 -12 -14 -15 and -16) 53.93 (C-13) 60.47 (C-8) 63.28 (C-6) 69.86 71.75 72.05 and 72.84 (C-2 -3 -4 and -5) 75.30 (C-7) 98.53 (C-1) 128.10 128.17 128.26 128.60 128.64 128.90 129.12 129.52 129.60 129.70 133.08 and 133.37 (4 times; Ph) 164.75 165.15 165.68 and 165.90 (CO2) and 216.57 (CO).(1R*,2R*,6S*)-2-(middot;-D-Glucopyranosyloxy)bicyclo4.4.1- undecan-11-one 11ab The same procedure described for compounds 9ab was used starting from a compounds 7ab (250 mg 0.74 mmol) to yield two diastereoisomers separated by flash chromatography (CH2Cl2ndash;MeOH 94 6) tetraols 11a and 11b (247 mg 97) as a gum in the ratio 55 45. Compound 11a nmax(KBr)/cm21 3419 2929 2872 1732 1682 1470 1445 1412 1361 1279 1200 1185 1147 1112 1076 1050 1026 and 990; aD 30 1157 (c 0.4 CH2Cl2); dH(250 MHz; D2O) 1.15ndash;2.23 (m 14 H 9- 10- 11- 12- 14- 15- and 16-H2) 2.73ndash;2.90 (m 1 H 13-H) 2.95ndash;3.12 (m 1 H 8-H) 3.39 (dd J 10 and 10 1 H 6-H) 3.51 (dd J 4 and 10 1 H 6-H9) 3.60ndash;3.92 (m 4 H 2- 3- 4- and 5-H) 4.01ndash;4.17 (m 1 H 7-H) and 5.01 (d J 4 1 H 1-H); dC(62 MHz; D2O) 21.15 25.16 25.39 25.84 26.37 29.85 and 32.97 (C-9 -10 -11 -12 -14 -15 and -16) 55.01 (C-13) 59.77 (C-8) 60.57 (C-6) 69.63 71.81 72.33 and 73.22 (C-2 -3 -4 and -5) 77.44 (C-7) 98.55 (C-1) and 219.40 (CO).Compound 11b mp 65ndash;68 8C (foam with CH2Cl2); nmax(KBr)/cm21 3379 2928 2865 1687 1451 1412 1358 1275 1233 1197 1183 1147 1101 1066 1050 and 1028; aD 28 195 (c 1.0 CH2Cl2); dH(250 MHz; D2O) 1.27ndash;2.19 (m 14 H 9- 10- 11- 12- 14- 15- and 16-H2) 2.71ndash;2.84 (m 1 H 13-H) 2.85ndash; 2.96 (m 1 H 8-H) 3.35ndash;3.94 (m 6 H 2- 3- 4- and 5-H and 6-H2) 4.24 (t J 4 1 H 7-H) and 5.06 (d J 4 1 H 1-H); dC(62 MHz; D2O) 21.07 25.41 25.80 26.71 27.95 28.86 and 31.09 (C-9 -10 -11 -12 -14 -15 and -16) 54.77 (C-13) 60.53 (C-8) 61.05 (C-6) 69.62 71.23 72.47 and 72.96 (C-2 -3 -4 and -5) 73.94 (C-7) 95.74 (C-1) and 219.44 (CO).(1R*,2R*,6S*)-2-(2,3,4,6-Tetra-O-benzoyl-middot;-D-glucopyranosyloxy) bicyclo4.4.1undecan-11-one 12a and 12b Using the same procedure which allowed us to obtain benzoylated compound 10a the diastereoisomers 11a (90 mg 0.26 mmol) and 11b (80 mg 0.23 mmol) gave respectively compounds 12a (159 mg 81) and 12b (110 mg 63) each as a powder. Compound 12a mp 169ndash;170 8C (Found C 70.7; H 6.0. C45H44O11 requires C 71.0; H 5.8); nmax(KBr)/cm21 3432 3063 2927 2855 1719 1692 1602 1584 1492 1451 1315 1273 1177 1095 1069 and 1027; aD 25 169 (c 1.0 25 CH2Cl2); dH(250 MHz; CDCl3) 0.99ndash;1.89 and 2.18ndash;2.33 (2 m 14 H 9- 10- 11- 12- 14- 15- and 16-H2) 2.53ndash;2.67 (m 1 H 13-H) 2.87ndash;2.99 (m 1 H 8-H) 4.03ndash;4.16 (br t J 8 1 H 7-H) 4.42ndash; 4.62 (m 3 H 5-H and 6-H2) 5.23 (dd J 4 and 10 1 H 2-H) 5.59 (d J 4 1 H 1-H) 5.56ndash;5.70 (m 1 H 4-H) 6.14 (t J 10 1 H 3-H) and 7.20ndash;7.60 and 7.81ndash;8.08 (2 m 20 H 4 times; Ph); dC(62 MHz; CDCl3) 21.80 25.66 26.29 26.73 27.40 30.37 and 34.50 (C-9 -10 -11 -12 -14 -15 and -16) 53.94 (C-13) 60.40 (C-8) 63.17 (C-6) 68.17 69.48 70.20 and 72.33 (C-2 -3 -4 and -5) 79.13 (C-7) 96.81 (C-1) 128.28 128.38 128.73 128.81 129.10 129.66 129.83 129.89 133.13 and 133.45 (4 times; Ph) 165.36 165.70 165.88 and 166.09 (CO2) and 216.05 (CO).Compound 12b mp 89ndash;90 8C (Found C 71.2; H 6.0); nmax(KBr)/cm21 3442 3063 2928 2859 1731 1692 1602 1584 1492 1452 1315 1273 1177 1094 1068 and 1026; aD 27 173 (c 0.95 CH2Cl2); dH(250 MHz; CDCl3) 1.20ndash;1.90 (m 14 H 9- 10- 11- 12- 14- 15- and 16-H2) 2.71ndash;2.87 (m 1 H 13-H) 2.98ndash;3.12 (m 1 H 8-H) 3.95ndash;4.08 (m 1 H 7-H) 4.50 (dd J 5 and 12 1 H 6-H) 4.68 (dd J 2 and 12 1 H 6-H9) 4.68ndash;4.83 (m 1 H 5-H) 5.25 (dd J 8 and 10 1 H 2-H) 5.46 (d J 8 1 H 1-H) 5.71 (t J 10 1 H 4-H) 6.10 (t J 10 1 H 3-H) and 7.15ndash; 7.62 and 7.82ndash;8.14 (2 m 20 H 4 times; Ph); dC(62 MHz; CDCl3) 21.31 25.90 26.15 26.79 28.20 29.23 and 32.57 (C-9 -10 -11 -12 -14 -15 and -16) 54.20 (C-13) 60.76 (C-8) 62.97 (C-6) 68.40 69.17 70.46 and 72.11 (C-2 -3 -4 and -5) 77.60 (C-7), J. Chem.Soc. Perkin Trans. 1 1997 2867 95.59 (C-1) 128.24 128.35 128.82 129.68 129.67 129.75 129.95 133.05 and 133.43 (4 times; Ph) 165.36 165.59 165.83 and 166.19 (CO2) and 215.72 (CO). 2-Hydroxybicyclo4.4.1undecan-11-one 13 4a Compounds 9ab (154 mg 0.447 mmol) and sulfuric acid (0.5 M; 4.5 cm3) were heated at 100 8C for 8 h. After the mixture had cooled to room temperature aq. KHCO3 (10) was added to neutralize it. The aqueous phase was extracted with dichloromethane (3 times; 5 cm3) and the combined organic extract was washed with water (5 cm3) dried over MgSO4 and concentrated under reduced pressure. Flash chromatography of the residue (hexanendash;ethyl acetate 7 3) gave keto alcohol 13 (38 mg 47). Using the same methodology acidic hydrolysis of glycosides 11ab (210 mg 0.61 mmol) for 11 h gave the same keto alcohol 13 (46 mg 42).Similar treatment for each of the two diastereoisomers 11a and 11b allowed us to measure the rotation of enantiomerically pure materials. Isomer 11a gave compound (2)-13 aD 26 29 (c 0.6 CH2Cl2) and isomer 11b gave compound (1)-13 aD 27 19 (c 0.55 CH2Cl2); (1)-13 nmax(neat)/cm21 3446 3019 2932 2858 1684 1518 1441 1215 1122 and 1035; dH(200 MHz; CDCl2) 1.22ndash;1.98 (m 14 H 3- 4- 5- 7- 8- 9- and 10-H2) 2.04ndash;2.30 (br s 1 H OH) 2.68ndash;2.87 (m 2 H 1- and 6-H) and 4.04 (m 1 H 2-H); dC(50 MHz; CDCl3) 21.0 26.0 26.34 26.40 27.60 29.24 and 35.23 (C-3 -4 -5 -7 -8 -9 and -10) 54.69 (C-6) 62.49 (C-1) 69.33 (C-2) and 217.78 (CO). 2-(2-Oxobicyclo3.2.2nona-3,8-dien-6-yl)acetaldehyde 15ab A solution of compounds 4ab (400 mg 1.18 mmol) in sulfuric acid (0.5 M; 15 cm3) was heated at 80 8C for 2.5 h.After cooling to room temperature the reaction mixture was neutralized with aq. KHCO3 (10). The aqueous phase was extracted with dichloromethane (2 times; 10 cm3) and the combined organic phase was washed with water (5 cm3) dried over MgSO4 and concentrated. This oil was purified by flash chromatography over silica gel (hexanendash;ethyl acetate 6 4) to give compounds 15ab (57 mg 31) (in a 70 30 ratio) and hemiacetals 16ab (25 mg 13) (in a 25 75 ratio). Compounds 15ab (Found C 73.1; H 7.0. C11H12O2?0.25 H2O requires C 73.1; H 7.0); nmax(neat)/cm21 3020 2930 1736 1710 1677 1668 1520 1422 1215 and 1022. Compound 15a dH(250 MHz; CDCl3) 1.50 (ddd J 4 6 and 14 1 H 14-Hexo) 2.27 (ddd J 1 10 and 14 1 H 14-Hendo) 2.50ndash; 2.59 (m 2 H 16-H2) 2.77ndash;2.90 (m 1 H 15-H) 3.16 (br t 1 H J 8 10-H) 3.48 (m 1 H 13-H) 5.79 (dd J 2 and 11 1 H 8-H) 6.20 (t 1 H 12-H) 6.42 (t 1 H 11-H) 7.12 (dd J 9 and 11 1 H 9-H) and 9.75 (t J 1 1 H CHO); dC(50 MHz; CDCl3) 28.92 (C-14) 33.14 (C-15) 41.53 (C-10) 52.08 (C-13 and -16) 128.35 and 129.86 (C-11 and -12) 135.55 (C-8) 152.87 (C-9) 197.57 (CO) and 200.99 (CHO).Compound 15b dH(250 MHz; CDCl3) 1.38 (ddd J 3 6 and 14 1 H 14-Hendo) 2.44 (ddd J 1 7 and 14 1 H 14-Hexo) 2.50ndash; 2.59 (m 2 H 16-H2) 2.77ndash;2.90 (m 1 H 15-H) 3.31 (br t J 8 1 H 10-H) 3.48 (m 1 H 13-H) 5.90 (dd J 2 and 11 1 H 8-H) 6.05 (t J 8 1 H 12-H) 6.60 (t J 8 1 H 11-H) 6.86 (dd J 9 and 11 1 H 9-H) and 9.80 (t J 1 1 H CHO); dC(50 MHz; CDCl3) 28.04 (C-14) 34.26 (C-15) 41.27 (C-10) 49.86 (C-16) 51.79 (C-13) 125.69 and 131.44 (C-11 and -12) 139.49 (C-8) 149.70 (C-9) 196.64 (CO) and 200.74 (CHO).Compounds 16ab (Found C 67.6; H 7.0. C11H14O3 requires C 68.0; H 7.3); mp 102 8C; nmax(KBr)/cm21 3389 3019 2932 1700 1685 1216 1157 1085 and 1046; m/z 194 (M1 1.7) 176 (M1 2 H2O 7.2) 150 (7) 105 (41) 91 (86) 79 (100) 78 (68) and 65 (12). Compound 16a dH(250 MHz; CDCl3) 1.60 (ddd J 3 13 and 13 1 H 14-H) 1.67 (ddd J 5 9 and 13 1 H 16-H) 1.89 (ddd J 3 5 and 13 1 H 16-H9) 2.26 (ddd J 3 6 and 13 2 H 14-H9 and 15-H) 2.53 (d J 17 1 H 8-H) 2.86ndash;3.02 (m 1 H 10-H) 3.13 (dd J 8 and 17 1 H 8-H9) 3.23 (br t J 6 1 H 13-H) 4.10 (br s 1 H OH) 4.47 (br t J 8 1 H 9-H) 4.86 (dd J 1 and 9 1 H 7-H) 6.17 (dt J 6 and 8 1 H 12-H) and 6.34 (dt J 6 and 8 1 H 11-H); dC(62 MHz; CDCl3) 28.42 (C-15) 32.29 (C-14) 36.61 (C-10) 37.30 (C-16) 46.70 (C-8) 50.84 (C-13) 70.54 (C-9) 87.49 (C-7) 130.94 and 133.33 (C-11 and -12) and 211.75 (CO).Compound 16b dH(200 MHz; CDCl3) 1.51ndash;1.71 (m 1 H 14-H) 1.82ndash;2.12 (m 2 H 16-H2) 2.34ndash;2.42 (m 2 H 14-H9 and 15-H) 2.56 (d J 17 1 H 8-H) 2.86ndash;3.02 (m 1 H 10-H) 3.02 (dd J 9 and 17 1 H 8-H9) 3.23 (br t J 6 1 H 13-H) 3.81 (br s 1 H OH) 4.32 (br t J 8 1 H 9-H) 5.30 (d 1 H 7-H) 6.17 (dt J 6 and 8 1 H 12-H) and 6.34 (dt J 6 and 8 1 H 11-H); dC(62 MHz; CDCl3) 25.07 (C-15) 30.77 (C-14) 34.01 (C-16) 36.79 (C-10) 48.05 (C-8) 51.04 (C-13) 66.69 (C-9) 90.70 (C-7) 131.45 and 133.53 (C-11 and -12) and 210.21 (CO). Acknowledgements We thank C.N.R.S. and Universiteacute; Paris-Sud for financial support. References 1 J. H. Rigby T. L. Moore and S. Rege J. Org. Chem. 1986 51 2398; J. H. Rigby and S. V. Cuisiat J. Org. Chem. 1993 58 6286; J. H.Rigby 4 1 4 and 6 1 4 Cycloadditions in Comprehensive Organic Synthesis ed. B. M. Trost and I. Fleming Pergamon Press Oxford 1991 pp. 1063ndash;1109. 2 (a) S. Itocirc; Y. Fujise T. Okuda and Y. Inoue Bull. Chem. Soc. Jpn. 1966 39 1351; (b) R. C. Cookson B. V. Drake J. Hudec and A. Morrison Chem. Comm. 1966 15. 3 R. Hoffmann and R. B. Woodward J. Am. Chem. Soc. 1965 87 2046 4388. 4 (a) M. E. Garst V. A. Roberts and C. Prussin J. Org. Chem. 1982 47 3969; (b) M. E. Garst V. A. Roberts K. N. Houk and N. G. Rondan J. Am. Chem. Soc. 1984 106 3882. 5 (a) S. Itocirc; K. Sakan and Y. Fujise Tetrahedron Lett. 1970 2873; (b) M. E. Garst V. A. Roberts and C. Prussin Tetrahedron 1983 39 581 and references therein; (c) K. N. Houk and R. B. Woodward J. Am. Chem. Soc. 1970 92 4145. 6 M. F. Neuman and D. Martina Tetrahedron Lett.1977 2293. 7 (a) A. Lubineau J. Augeacute; and N. Lubin J. Chem. Soc. Perkin Trans. 1 1990 3011; (b) A. Lubineau and Y. Queneau J. Org. Chem. 1987 52 1001. 8 A. Lubineau and Y. Queneau Tetrahedron Lett. 1985 26 2653. For relevent studies on asymmetric Dielsndash;Alder reactions using chiral diene derivatives from carbohydrates see R. C. Gupta P. A. Harland and R. J. Stoodley J. Chem. Soc. Chem. Commun. 1983 754; A. Lubineau J. Augeacute; H. Bienaymeacute; N. Lubin and Y. Queneau Cycloaddition Reactions in Carbohydrate Chemistry ed. R. M. Giuliano ASC Symposium Series 1992 vol. 494 p. 147. 9 D. C. Rideout and R. Breslow J. Am. Chem. Soc. 1980 102 7816; P. A. Grieco P. Garner and Z. M. He Tetrahedron Lett. 1983 24 1897; A. Lubineau J. Augeacute; and Y. Queneau Synthesis 1994 741. 10 A. Lubineau J.Augeacute; H. Bienaymeacute; Y. Queneau and M. C. Scherrmann Carbohydrates as Organic Raw Materials II ed. G. Descotes VCH Weinheim Germany 1993 p. 99; A. Lubineau H. Bienaymeacute; Y. Queneau and M. C. Scherrmann New J. Chem. 1994 18 279. Paper 7/02447I Received 10th April 1997 Accepted 2nd June 1997 J. Chem. Soc. Perkin Trans. 1 1997 2863 Aqueous 6 1 4 cycloadditions of tropone with 1-(glucopyranosyloxy) buta-1,3-diene Andreacute; Lubineau a Giliane Bouchain a and Yves Queneau a,b a Laboratoire de Chimie Organique Multifonctionnelle CNRS URA 462 Institut de Chimie Moleacute;culaire drsquo;Orsay Universiteacute; de Paris-Sud Bat. 420 91405 Orsay Cedex France b Present address Uniteacute; Mixte de Sucrochimie CNRS-Beacute;ghin-Say (UMR 143) c/o Eridania Beacute;ghin-Say CEI 27 Bd du 11 novembre 1918 BP 2132 69603 Villeurbanne Cedex France The first aqueous 6 1 4 cycloaddition reaction is reported.Starting from tropone and glucopyranosyloxybuta- 1,3-diene bicyclic adducts arising from the expected exo-transition state have been obtained in fair yields under much milder conditions than those usually required thus preventing side-4 1 2 adduct formation by limiting the reversibility of the 6 1 4 process. Influence of the solvent is clearly demonstrated as the reaction in methanol is much slower compared with that in water. The best yields are obtained in buffered solutions or in concentrated aq. sugar solutions. Introduction The 6 1 4 cycloaddition reaction of tropone with dienes allows the construction of the bicyclo4.4.1undecanone backbone which can serve as the starting point for the synthesis of complex polycyclic compounds such as troponophanes cyclodecenes and some diterpenes in the ingenol series.1 This reaction was first reported in the mid 60s in the case of cyclopentadiene which provided exo-oriented adducts 2 as predicted by the Woodwardndash;Hoffmann rules.3 The condensation of non-substituted tropone with simple dienes is not an easy process as confirmed by the high temperature and long reaction time which are often necessary.4 Owing to the greater reversibility of the 6 1 4 cycloaddition pathway compared with the 4 1 2 one 4 1 2 adducts can be the major products upon prolongation of the reaction time.5 It is therefore useful to investigate new conditions for such reactions.A possibility is to catalyse the reaction using transition metal catalysts.6 Based on our experience in cycloadditions using water as the solvent,7 we studied the outcome of the reaction of tropone in aqueous medium using the water-soluble 1-(b-D-glucopyranosyloxy)- buta-1,3-diene 1.8 Indeed we showed that in water such a diene could provide 4 1 2 cycloaddition adducts with both rate and selectivity increase compared with other solvents.9 Widening the scope of the use of this diene in aqueous medium we report herein the synthesis of 2-(glucopyranosyloxy)- bicyclo4.4.1undecanones as the first 6 1 4 cycloaddition reaction performed in water.Results and discussion Cycloaddition of b-D-glucopyranosyloxybuta-1,3-diene 1 with cyclohepta-2,4,6-trienone (tropone) 3 was performed in aqueous medium to provide adducts 4ab as a mixture of two diastereoisomers in nearly equivalent amounts (Scheme 1) which were characterized as their per-acetylated derivatives 5ab.The relative stereochemistry in adducts 4ab was assigned by comparison with known derivatives after reduction and hydrolysis (vide infra). Reaction conditions and yields are given in Table 1. The necessity of keeping the temperature below 60 8C to prevent substantial hydrolysis of the starting diene led to quite long reaction times. This had a positive consequence for the 6 1 4 process whose reversibility was inhibited therefore preventing side-4 1 2 cycloadditions to occur. Nevertheless moderate to fair yields of adducts 4ab could be obtained at 40 or 50 8C which is an exceptionally low temperature for a 6 1 4 cycloaddition. For example a temperature of 80 8C is necessary for reaction of cyclopentadiene,2a although a much more reactive diene and refluxing xylene during 5 days is necessary for the cycloaddition with 1-acetoxybuta-1,3-diene.4a The reaction Scheme 1 Reagents and yields i see Table 1; ii Ac2O Py (96); iii 3 water (66); iv Ac2O Py (92).Arbitrary NMR numbering scheme is shown for structures 4 and 5. O + O RO RO OR OR O 3 O RO RO OR OR O H O 13 14 15 16 7 12 11 10 9 8 O RO RO OR OR O H O + i 4ab R = H 5ab R = Ac ii O HO HO OH OH O iii O RO RO OR OR O H O O RO RO OR OR O H O 7ab R = H 8ab R = Ac iv + 1 R = H 2 R = Ac 6 2864 J. Chem. Soc. Perkin Trans. 1 1997 Table 1 Reaction conditions and yields for adducts 4ab and 7ab (Scheme 1) Entry 1 2 3 4 5 6 7 8 9 10 Diene (mol equiv.) 1 (0.5) 1 (0.5) 2 (0.5) 1 (0.5) 1 (0.5) 1 (2.0) 1 (1.8) 1 (0.5) 1 (0.5) 6 (1.8) Solvent water methanol toluene water pH 7 buffer pH 7 buffer pH 7 buffer 1 hydroquinone 4 M glucose 2.5 M sucrose pH 7 buffer 1 hydroquinone T/8C 40 40 110 50 50 50 50 40 40 50 t/days 9.5 12 10 3.5 6.5 6.5 6.5 9.5 9.5 6.5 Yield () 45 28 44 46 54 58 62 62 59 66 of diene 1 with tropone 3 was shown to be very sensitive to the nature of the solvent as a much lower yield was obtained in methanol (entry 2) and a much slower reaction was observed for the acetylated diene 2 in toluene (entry 3).Yields could be improved by conducting the reaction in water at 50 8C in the presence of additives (entries 5ndash;7) such as (i) pH 7 phosphate buffer in order to prevent competitive hydrolysis of diene and (ii) hydroquinone to inhibit polymerization of diene. Concentrated glucose and sucrose as aqueous solutions were also used (entries 8 and 9) for which yields of ~60 were obtained.We have already described the use of such a solvent mixture for Dielsndash;Alder reactions and other transformations.10 It was shown that the rate increase was due to enforced hydrophobic effects. The a-glucosyl diene 6 was also shown to provide similar adducts 7ab which were characterized as their per-acetylated derivatives 8ab. In order to establish the stereochemistry (exo) of the glycosylated bicyclo4.4.1undecanones compounds 4ab were submitted to hydrolysis. As alcohol 13 has already been described in the literature,4a adducts 4ab were hydrogenated under classical conditions (10 Pd/C 14 psi H2) to provide compounds 9ab which were characterized as their benzoylated derivatives 10ab (Scheme 2).It is to be noted that at this stage the two diastereoisomers 9ab could be separated by flash chromatography but attempts to establish the absolute configuration at the newly created chiral centres were unsuccessful. The same synthetic sequence was applied to the a-anomers 7ab allowing isolation of hydrogenated glycosides 11ab and their benzoylated derivatives 12ab. Acidic hydrolysis (0.5 M H2SO4; 100 8C) of glycosides 9ab albeit in moderate yield (47) allowed us to identify keto alcohol 13 (by comparison with literature NMR data) as the sole product thus confirming the total exo selectivity of the cycloaddition. Similar treatment of each of the two compounds 9a and 9b as pure isomers allowed us to obtain (1)-13 and (2)-13 for which an aD value of 19 and 29 were measured.Hydrogenated adducts in the a series 7ab could be hydrolysed to provide 13 in similar yield (42). Direct hydrolysis of adducts without previous hydrogenation of the three double bonds appeared to be a much more complicated process. Indeed intermediate keto alcohols (such as that having structure 14) could not be isolated before subsequent oxy-Cope3,3 sigmatropic rearrangement as shown by isolation of structures 15ab (31) after acidic treatment (0.5 M H2SO4; 80 8C) together with hemiacetals 16ab (13) arising from hydration of one of compounds 15ab having a cis relationship between the oxoethyl chain and the enone bridge. Their structures were determined by 1H COSY NMR analysis. A similar oxycope rearrangement has already been described in the literature.5b Conclusions In this paper we have reported the first aqueous 6 1 4 cycloaddition of tropone using water-soluble dienes derived from carbohydrates.The reaction was shown to proceed at much lower temperature compared with the usual conditions providing fair yields of glycosylated bicyclo4.4.1undecanones. The exo selectivity was confirmed after hydrogenation and hydrolysis and pure enantiomers of 7-hydroxybicyclo4.4.1- undecanone 13 could be isolated. Experimental General NMR spectra were recorded with Bruker AC200 and 250 spectrometers. d-Values are given in ppm downfield from internal Scheme 2 Reagents and yields i H2 Pd/C MeOH (98); ii BzCl Py; iii H2 Pd/C MeOH (97); iv 0.5 M H2SO4 O RO RO OR OR O H O RO RO OR OR O H O O RO RO OR OR O H O 4ab O RO RO OR OR O H O 13 14 15 16 7 12 11 10 9 8 9ab R = H 10ab R = Bz ii + i 7ab iii + 11ab R = H 12ab R = Bz ii O H HO 9ab iv O H HO (plusmn;)-13 14 O CHO H O H CHO H O O OH 17 8 9 12 11 10 15 16 7 14 14 17 8 9 12 11 10 15 16 7 13 13 15ab 16ab + J.Chem. Soc. Perkin Trans. 1 1997 2865 tetramethylsilane and J-values are given in Hz. Carbohydrate entities are described with the classical numbering. Position 7 is arbitrarily assigned to the bicyclic ringrsquo;s carbon linked to oxygen. Positions 8 and 13 are assigned to the ring junction. IR spectra were recorded using a Bruker FT instrument. Flash chromatography was performed using 6ndash;35 mm silica gel (60) purchased from S.D.S. TLC was performed using Merck 60 F254 plates and visualized first with UV light and then by heating after treatment with alcoholic sulfuric acid. Elementary analyses were performed at the Service Central de Microanalyse du C.N.R.S.Optical rotations were measured on a JASCO (DIP- 370) spectrometer with aD-values given in units of 1021 deg cm2 g21. (1R*,6R*,7R*)-7-(lsquor;-D-Glucopyranosyloxy)bicyclo4.4.1- undeca-2,4,8-trien-11-one 4ab b-D-Glucopyranosyloxybuta-1,3-diene 1 8 (1.89 g 8.1 mmol) tropone 3 (1.42 cm3 14.65 mmol) and hydroquinone (10 mg 0.09 mmol) were heated in phosphate buffer (1 M pH 7; 16.2 cm3) at 50 8C for 6 days. After being cooled to room temperature the mixture was diluted with water (3 cm3) and extracted with dichloromethane (2 times; 3 cm3). The aqueous layer was concentrated under reduced pressure. The residue was purified by flash chromatography (CH2Cl2ndash;MeOH 94 6) to give compounds 4ab (1.7 g 62) as a syrup (Found C 58.1; H 6.7.C17H22O7?0.66H2O requires C 58.3; H 6.7). Isomer 4a dH(250 MHz; D2O) 2.52ndash;2.74 (2 m 2 H 14-H2) 3.22ndash;4.0 (m 8 H 2- 3- 4- 5- 8- and 13-H and 6-H2) 4.52 (d J 8 1 H 1-H) 4.94ndash;5.05 (m 1 H 7-H) 5.69ndash;6.02 (m 4 H 9- 12- 15- and 16-H) and 6.12ndash;6.36 (m 2 H 10- and 11-H); dC(62 MHz; D2O) 29.23 (C-14) 54.94 (C-13) 60.64 (C-6) 62.47 (C-8) 69.58 72.95 74.18 75.74 75.87 (C-2 -3 -4 -5 and -7) 100.96 (C-1) 124.25 125.71 127.53 130.22 130.38 and 131.41 (C-9 -10 -11 -12 -15 and -16) and 209.73 (CO). Isomer 4b dH(250 MHz; D2O) 2.56ndash;2.67 (2 m 2 H 14-H2) 3.15ndash;3.97 (m 8 H 2- 3- 4- 5- 8- and 13-H and 6-H2) 4.61 (d J 8 1 H 1-H) 4.95ndash;5.09 (m 1 H 7-H) 5.74ndash;5.90 (m 4 H 9- 12- 15- and 16-H) and 6.18ndash;6.36 (m 2 H 10- and 11-H); dC(62 MHz; D2O) 29.25 (C-14) 54.76 (C-13) 60.59 (C-6) 61.62 (C-8) 69.53 73.18 75.50 and 76.0 (C-2 -3 -4 -5 and -7) 102.28 (C-1) 124.95 126.53 128.14 129.65 130.65 and 132.21 (C-9 -10 -11 -12 -15 and -16) and 208.17 (CO).(1R*,6R*,7R*)-7-(2,3,4,6-Tetra-O-acetyl-lsquor;-D-glucopyranosyloxy) bicyclo4.4.1undeca-2,4,8-trien-11-one 5ab To a stirred solution of glucosylated compounds 4ab (45 mg 0.13 mmol) in pyridine (0.16 cm3) cooled to 0 8C and under nitrogen was added acetic anhydride (0.11 cm3 1.22 mmol). The reaction mixture was stirred for 12 h before removal of the solvent under reduced pressure to leave a crude product as a yellow oil. This oil was recrystallized in diethyl ether to give compounds 5ab (63 mg 96) as a solid (Found C 59.0; H 6.1. C25H30O11 requires C 59.3; H 6.0). The two diastereoisomers have been partially separated then deacetylated to give tetraols 4a and 4b.Isomer 5a (Found C 58.8; H 6.1); mp 116ndash;117 8C; nmax(neat)/cm21 3022 1758 1709 1522 1427 1368 1215 1041 and 929; aD 27 14 (c 0.45 CH2Cl2); dH(250 MHz; CDCl3) 2.0 2.01 and 2.10 (4 s 12 H CH3) 2.35ndash;2.52 (m 1 H 14-H) 2.59ndash;2.75 (m 1 H 14-H9) 3.40ndash;3.50 (m 1 H 13-H) 3.59ndash;3.69 (m 1 H 5-H) 3.70ndash;3.79 (dt J 1 and 8 1 H 8-H) 4.15 (dd J 2 and 12 1 H 6-H) 4.20 (dd J 5 and 12 1 H 6-H9) 4.51 (d J 8 1 H 1-H) 4.72ndash;4.82 (m 1 H 7-H) 4.91ndash;5.23 (m 3 H 2- 3- and 4-H) 5.49ndash;5.60 and 5.61ndash;5.86 (2 m 4 H 9- 12- 15- and 16-H) and 6.01ndash;6.13 (m 2 H 10- and 11-H); dC(62 MHz; CDCl3) 20.56 and 20.69 (4 times; CH3) 31.30 (C-14) 54.49 (C-13) 60.07 (C-6) 62.96 (C-8) 68.46 71.26 71.79 and 72.73 (C-2 -3 -4 and -5) 74.39 (C-7) 99.12 (C-1) 125.68 125.77 126.88 130.07 131.30 and 132.20 (C-9 -10 -11 -12 -15 and -16) 169.03 169.32 170.27 and 170.51 (CO2) and 203.21 (CO).Isomer 5b (Found C 59.0; H 5.95); aD 28 229 (c 0.7 CH2Cl2); mp 166ndash;167 8C; nmax(neat)/cm21 3022 1757 1711 1522 1424 1366 1215 1040 and 929; dH(250 MHz; CDCl3) 2.0 2.04 and 2.10 (4 s 12 H CH3) 2.37ndash;2.52 (m 1 H 14-H) 2.58ndash; 2.75 (m 1 H 14-H9) 3.43ndash;3.54 (m 1 H 13-H) 3.58ndash;3.72 (2 m 2 H 5- and 8-H) 4.12 (dd 1 H J 2 and 12 6-H) 4.26 (dd 1 H J 5 and 12 6-H9) 4.59 (d J 8 1 H 1-H) 4.73ndash;4.84 (m 1 H 7-H) 4.97 (dt J 8 and 10 1 H 2-H) 5.08 (t 1 H J 10 4-H) 5.20 (t 1 H J 10 3-H) 5.55ndash;5.78 and 5.80ndash;5.92 (2 m 4 H 9- 12- 15- and 16-H) and 6.03ndash;6.19 (m 2 H 10- and 11-H); dC(62 MHz; CDCl3) 20.59 20.61 20.71 and 20.74 (CH3) 30.98 (C-14) 54.55 (C-13) 61.87 (C-6) 62.27 (C-8) 68.34 71.18 71.74 and 72.62 (C-2 -3 -4 and -5) 75.65 (C-7) 100.62 (C-1) 125.71 127.60 128.22 132.15 and 133.32 (C-9 -10 -11 -12 -15 and -16) 169.27 169.39 170.30 and 170.65 (CO2) and 202.58 (CO).Starting from the acetylated diene 27b (20 mg 0.05 mmol) as a solution in toluene (0.1 cm3) with tropone (0.01 cm3 0.1 mmol) the reaction mixture was heated at reflux for 10 days. Removal of the solvent followed by flash chromatography (hexanendash;ethyl acetate 7 3) yielded adducts 5ab (11 mg 44). (1R*,6R*,7R*)-7-(2,3,4,6-Tetra-O-acetyl-middot;-D-glucopyranosyloxy) bicyclo4.4.1undeca-2,4,8-trien-11-one 8ab The same procedure described for anomers 4ab was used starting from a-D-glucopyranosyloxybuta-1,3-diene 68 (2 g 8.6 mmol) and tropone 3 (1.5 cm3 15.8 mmol) in phosphate buffer (17.2 cm3). Compounds 7ab {7-(a-D-glucopyranosyloxy)- bicyclo4.4.1undeca-2,4,8-trien-11-one} (1.9 g 66) were obtained as a syrup (ratio 55 45) (Found C 57.5; H 6.4.C17H22O7?0.83H2O requires C 57.8; H 6.7); nmax(KBr)/cm21 3388 3031 2929 1698 1407 1338 1259 1145 1076 and 1026; dH(250 MHz; D2O) 2.57ndash;2.67 (2 m 4 H 14-H2) 3.35ndash;3.90 (m 16 H 2- 3- 4- 5- 8- and 13-H and 6-H2) 4.80ndash;4.94 (m 2 H 7-H) 4.98 (d 1 H J 4 1-H) 5.10 (m 1 H J 4 1-H) 5.63ndash;5.96 (m 8 H 9- 12- 15- and 16-H) and 6.15ndash;6.32 (m 4 H 10- and 11-H); dC(62 MHz; D2O) 29.44 and 31.17 (C-14) 53.85 and 54.83 (C-13) 60.16 and 60.35 (C-6) 61.80 and 62.30 (C-8) 69.27 69.50 70.05 71.01 71.34 72.0 72.38 72.91 and 73.36 (C-2 -3 -4 -5 and -7) 96.09 and 98.58 (C-1) 124.70 125.30 126.16 128.05 128.47 129.70 130.64 131.61 131.95 and 132.42 (C-9 -10 -11 -12 -15 and -16) and 208.81 (CO). Further acetylation using the same procedure as for anomers 5ab led starting from tetraols 7ab (1.7 g 5 mmol) to acetylated derivatives 8ab (2.33 g 92) as a powder (Found C 58.4; H 6.0.C25H30O11?0.5H2O requires C 58.3; H 6.1); nmax(KBr)/cm21 1762 1760 1753 1749 1741 1254 1246 1239 1236 1229 1225 1217 and 1046; dH(250 MHz; CDCl3) 1.99ndash; 2.18 (m 24 H CH3) 2.33ndash;2.55 (m 2 H 14-H) 2.64ndash;2.85 (m 2 H 14-H9) 3.42ndash;3.58 (m 2 H 13-H) 3.60ndash;3.68 (dt 1 H J 2 and 8 8-H) 3.70ndash;3.80 (dt J 2 and 8 1 H 8-H) 3.96ndash;4.35 (m 6 H 5-H and 6-H2) 4.68ndash;4.89 (m 2 H 7-H) 4.98ndash;5.53 (m 8 H 1- 2- 3- and 4-H) 5.53ndash;5.90 (m 8 H 9- 12- 15- and 16-H) and 6.02ndash;6.20 (m 4 H 10- and 11-H); dC(62 MHz; CDCl3) 20.63 (8 times; CH3) 30.58 and 31.32 (C-14) 54.29 and 54.81 (C-13) 61.64 (2 times; C-6) 61.98 and 62.40 (C-8) 67.48 67.70 68.27 68.49 70.03 and 70.70 (2 times; C-2 -3 -4 and -5) 72.59 and 73.86 (C-7) 94.45 and 95.62 (C-1) 125.09 125.43 125.73 127.68 129.75 131.60 132.10 and 132.55 (C-9 -10 -11 -12 -15 and -16) 169.56 169.98 and 170.53 (8 times; CO2) and 202.60 and 202.71 (CO).(1R*,2R*,6S*)-2-(2,3,4,6-Tetra-O-benzoyl-lsquor;-D-glucopyranosyloxy) bicyclo4.4.1undecan-11-one 10a and 10b A solution of adducts 4ab (250 mg 0.74 mmol) and 150 mg of 10 palladium on carbon in 5 cm3 of methanol were placed under 14 psi of hydrogen and the mixture was shaken for 24 h. The suspension was filtered through Celite and the filtrate was concentrated under reduced pressure. Separation of diastereoisomers was achieved by flash chromatography (CH2Cl2ndash; 2866 J. Chem. Soc. Perkin Trans. 1 1997 MeOH 94 6) to provide purified samples of compounds 9a and 9b {2-(b-D-glucopyranosyloxy)bicyclo4.4.1undecan-11- one} (250 mg 98) as a powder in a 55 45 ratio.Compound 9a mp 60ndash;62 8C; nmax(KBr)/cm21 3409 2927 2868 1681 1650 1445 1365 1278 1162 1076 1039 and 1010; aD 28 269 (c 1.04 CH2Cl2); dH(250 MHz; D2O) 1.15ndash;2.29 (m 14 H 9- 10- 11- 12- 14- 15- and 16-H2) 2.70ndash;2.87 (m 1 H 13-H) 2.92ndash;3.05 (m 1 H 8-H) 3.20ndash;3.57 (m 4 H 2- 3- 4- and 5-H) 3.72 (dd J 5 and 12 1 H 6-H) 3.85 (dd 1 H J 2 and 12 6-H9) 4.19ndash;4.30 (m 1 H 7-H) and 4.60 (d J 8 1 H 1-H); dC(62 MHz; D2O) 21.09 25.54 25.75 27.30 28.85 and 33.52 (C-9 -10 -11 -12 -14 -15 and -16) 54.93 (C-13) 60.12 (C-8) 60.76 (C-6) 69.65 73.41 75.62 and 75.99 (C-2 -3 -4 and -5) 78.91 (C-7) 102.65 (C-1) and 219.58 (CO). Compound 9b mp 68ndash;70 8C; nmax(KBr)/cm21 3409 2918 2867 1684 1456 1361 1186 1160 1078 and 1037; aD 26 223 (c 1 CH2Cl2); dH(250 MHz; D2O) 1.15ndash;2.30 (m 14 H 9- 10- 11- 12- 14- 15- and 16-H2) 2.70ndash;2.92 (m 2 H 13-H) 3.25 (t J 8 1 H 8-H) 3.18ndash;3.56 (m 4 H 2- 3- 4- and 5-H) 3.74 (dd J 5 and 12 1 H 6-H) 3.92 (dd J 1 and 12 1 H 6-H9) 4.32 (br t J 8 1 H 7-H) and 4.52 (d J 8 1 H 1-H); dC(62 MHz; D2O) 20.98 25.39 25.78 26.35 27.85 28.67 and 32.09 (C-9 -10 -11 -12 -14 -15 and -16) 54.79 (C-13) 60.66 (C-6) 60.96 (C-8) 69.67 72.93 75.82 and 75.92 (C-2 -3 -4 and -5) 76.31 (C-7) 100.41 (C-1) and 219.41 (CO).To a stirred solution of tetraol 9a (90 mg 0.26 mmol) in pyridine (0.53 cm3) was added benzoyl chloride (0.17 cm3 1.44 mmol). The reaction mixture was stirred for 2.5 h at room temperature under nitrogen. Benzoyl chloride in excess was quenched by 0.3 cm3 of methanol and then dichloromethane (5 cm3) and water (3 cm3) were added.The organic phase was washed successively with dil. aq. hydrochloric acid (3 cm3) and saturated aq. NaHCO3 (3 cm3) and was then dried over MgSO4. After filtration the solution was concentrated under reduced pressure to give a pale yellow syrup. Flash chromatography of the residue (toluenendash;diethyl ether 95 5) provided tetrabenzoate 10a (175 mg 88). Using the same procedure starting from the diastereoisomer 9b (96 mg 0.28 mmol) compound 10b (117 mg 56) was obtained. Compound 10a mp 87ndash;89 8C (Found C 71.1; H 5.8. C45H44O11 requires C 71.0; H 5.8); nmax(KBr)/cm21 3630 3536 3440 3063 2928 2857 1729 1692 1602 1584 1492 1452 1365 1267 1177 1111 1069 and 1027; aD 23 123 (c 1.1 CH2Cl2); dH(200 MHz; CDCl3) 0.80ndash;1.85 and 2.10ndash;2.27 (2 m 14 H 9- 10- 11- 12- 14- 15- and 16-H2) 2.50ndash;2.67 (m 1 H 13-H) 2.74ndash;2.88 (m 1 H 8-H) 4.10ndash;4.28 (m 2 H 5- and 7-H) 4.50 (dd J 6 and 12 1 H 6-H) 4.63 (dd J 3 and 12 1 H 6-H9) 5.04 (d J 8 1 H 1-H) 5.50 (dd J 8 and 10 1 H 2-H) 5.60 (t J 10 1 H 4-H) 5.93 (t J 10 1 H 3-H) and 7.14ndash;7.61 and 7.79ndash; 8.08 (2 m 20 H 4 times; Ph); dC(62 MHz; CDCl3) 21.55 25.90 26.17 26.98 27.15 30.0 34.60 (C-9 -10 -11 -12 -14 -15 and -16) 53.89 (C-13) 59.73 (C-8) 63.16 (C-6) 69.82 71.97 72.12 and 72.73 (C-2 -3 -4 and -5) 78.16 (C-7) 100.90 (C-1) 128.17 128.27 128.58 128.64 129.09 129.43 129.55 129.62 129.69 133.09 and 133.38 (4 times; Ph) 164.89 165.15 165.67 and 165.87 (CO2) and 215.82 (CO).Compound 10b mp 90ndash;92 8C (Found C 71.1; H 6.0); nmax(KBr)/cm21 3630 3550 3063 2928 2855 1736 1685 1602 1584 1492 1452 1358 1264 1177 1094 1061 and 1026; aD 27 25 (c 1.05 CH2Cl2); dH(250 MHz; CDCl3) 0.95ndash;2.17 (m 14 H 9- 10- 11- 12- 14- 15- and 16-H2) 2.55ndash;2.68 (m 1 H 13-H) 2.70ndash;2.82 (m 1 H 8-H) 4.15ndash;4.32 (m 2 H 5- and 7-H) 4.54 (dd J 6 and 12 1 H 6-H) 4.63 (dd J 3 and 12 1 H 6-H9) 4.92 (d J 8 1 H 1-H) 5.49 (dd J 8 and 10 1 H 2-H) 5.63 (t J 10 1 H 4-H) 5.93 (t J 10 1 H 3-H) and 7.01ndash;7.60 and 7.79ndash;8.09 (2 m 20 H 4 times; Ph); dC(62 MHz; CDCl3) 21.80 25.67 26.16 27.51 30.95 and 33.19 (C-9 -10 -11 -12 -14 -15 and -16) 53.93 (C-13) 60.47 (C-8) 63.28 (C-6) 69.86 71.75 72.05 and 72.84 (C-2 -3 -4 and -5) 75.30 (C-7) 98.53 (C-1) 128.10 128.17 128.26 128.60 128.64 128.90 129.12 129.52 129.60 129.70 133.08 and 133.37 (4 times; Ph) 164.75 165.15 165.68 and 165.90 (CO2) and 216.57 (CO).(1R*,2R*,6S*)-2-(middot;-D-Glucopyranosyloxy)bicyclo4.4.1- undecan-11-one 11ab The same procedure described for compounds 9ab was used starting from a compounds 7ab (250 mg 0.74 mmol) to yield two diastereoisomers separated by flash chromatography (CH2Cl2ndash;MeOH 94 6) tetraols 11a and 11b (247 mg 97) as a gum in the ratio 55 45.Compound 11a nmax(KBr)/cm21 3419 2929 2872 1732 1682 1470 1445 1412 1361 1279 1200 1185 1147 1112 1076 1050 1026 and 990; aD 30 1157 (c 0.4 CH2Cl2); dH(250 MHz; D2O) 1.15ndash;2.23 (m 14 H 9- 10- 11- 12- 14- 15- and 16-H2) 2.73ndash;2.90 (m 1 H 13-H) 2.95ndash;3.12 (m 1 H 8-H) 3.39 (dd J 10 and 10 1 H 6-H) 3.51 (dd J 4 and 10 1 H 6-H9) 3.60ndash;3.92 (m 4 H 2- 3- 4- and 5-H) 4.01ndash;4.17 (m 1 H 7-H) and 5.01 (d J 4 1 H 1-H); dC(62 MHz; D2O) 21.15 25.16 25.39 25.84 26.37 29.85 and 32.97 (C-9 -10 -11 -12 -14 -15 and -16) 55.01 (C-13) 59.77 (C-8) 60.57 (C-6) 69.63 71.81 72.33 and 73.22 (C-2 -3 -4 and -5) 77.44 (C-7) 98.55 (C-1) and 219.40 (CO).Compound 11b mp 65ndash;68 8C (foam with CH2Cl2); nmax(KBr)/cm21 3379 2928 2865 1687 1451 1412 1358 1275 1233 1197 1183 1147 1101 1066 1050 and 1028; aD 28 195 (c 1.0 CH2Cl2); dH(250 MHz; D2O) 1.27ndash;2.19 (m 14 H 9- 10- 11- 12- 14- 15- and 16-H2) 2.71ndash;2.84 (m 1 H 13-H) 2.85ndash; 2.96 (m 1 H 8-H) 3.35ndash;3.94 (m 6 H 2- 3- 4- and 5-H and 6-H2) 4.24 (t J 4 1 H 7-H) and 5.06 (d J 4 1 H 1-H); dC(62 MHz; D2O) 21.07 25.41 25.80 26.71 27.95 28.86 and 31.09 (C-9 -10 -11 -12 -14 -15 and -16) 54.77 (C-13) 60.53 (C-8) 61.05 (C-6) 69.62 71.23 72.47 and 72.96 (C-2 -3 -4 and -5) 73.94 (C-7) 95.74 (C-1) and 219.44 (CO). (1R*,2R*,6S*)-2-(2,3,4,6-Tetra-O-benzoyl-middot;-D-glucopyranosyloxy) bicyclo4.4.1undecan-11-one 12a and 12b Using the same procedure which allowed us to obtain benzoylated compound 10a the diastereoisomers 11a (90 mg 0.26 mmol) and 11b (80 mg 0.23 mmol) gave respectively compounds 12a (159 mg 81) and 12b (110 mg 63) each as a powder.Compound 12a mp 169ndash;170 8C (Found C 70.7; H 6.0. C45H44O11 requires C 71.0; H 5.8); nmax(KBr)/cm21 3432 3063 2927 2855 1719 1692 1602 1584 1492 1451 1315 1273 1177 1095 1069 and 1027; aD 25 169 (c 1.0 25 CH2Cl2); dH(250 MHz; CDCl3) 0.99ndash;1.89 and 2.18ndash;2.33 (2 m 14 H 9- 10- 11- 12- 14- 15- and 16-H2) 2.53ndash;2.67 (m 1 H 13-H) 2.87ndash;2.99 (m 1 H 8-H) 4.03ndash;4.16 (br t J 8 1 H 7-H) 4.42ndash; 4.62 (m 3 H 5-H and 6-H2) 5.23 (dd J 4 and 10 1 H 2-H) 5.59 (d J 4 1 H 1-H) 5.56ndash;5.70 (m 1 H 4-H) 6.14 (t J 10 1 H 3-H) and 7.20ndash;7.60 and 7.81ndash;8.08 (2 m 20 H 4 times; Ph); dC(62 MHz; CDCl3) 21.80 25.66 26.29 26.73 27.40 30.37 and 34.50 (C-9 -10 -11 -12 -14 -15 and -16) 53.94 (C-13) 60.40 (C-8) 63.17 (C-6) 68.17 69.48 70.20 and 72.33 (C-2 -3 -4 and -5) 79.13 (C-7) 96.81 (C-1) 128.28 128.38 128.73 128.81 129.10 129.66 129.83 129.89 133.13 and 133.45 (4 times; Ph) 165.36 165.70 165.88 and 166.09 (CO2) and 216.05 (CO).Compound 12b mp 89ndash;90 8C (Found C 71.2; H 6.0); nmax(KBr)/cm21 3442 3063 2928 2859 1731 1692 1602 1584 1492 1452 1315 1273 1177 1094 1068 and 1026; aD 27 173 (c 0.95 CH2Cl2); dH(250 MHz; CDCl3) 1.20ndash;1.90 (m 14 H 9- 10- 11- 12- 14- 15- and 16-H2) 2.71ndash;2.87 (m 1 H 13-H) 2.98ndash;3.12 (m 1 H 8-H) 3.95ndash;4.08 (m 1 H 7-H) 4.50 (dd J 5 and 12 1 H 6-H) 4.68 (dd J 2 and 12 1 H 6-H9) 4.68ndash;4.83 (m 1 H 5-H) 5.25 (dd J 8 and 10 1 H 2-H) 5.46 (d J 8 1 H 1-H) 5.71 (t J 10 1 H 4-H) 6.10 (t J 10 1 H 3-H) and 7.15ndash; 7.62 and 7.82ndash;8.14 (2 m 20 H 4 times; Ph); dC(62 MHz; CDCl3) 21.31 25.90 26.15 26.79 28.20 29.23 and 32.57 (C-9 -10 -11 -12 -14 -15 and -16) 54.20 (C-13) 60.76 (C-8) 62.97 (C-6) 68.40 69.17 70.46 and 72.11 (C-2 -3 -4 and -5) 77.60 (C-7), J.Chem. Soc. Perkin Trans. 1 1997 2867 95.59 (C-1) 128.24 128.35 128.82 129.68 129.67 129.75 129.95 133.05 and 133.43 (4 times; Ph) 165.36 165.59 165.83 and 166.19 (CO2) and 215.72 (CO). 2-Hydroxybicyclo4.4.1undecan-11-one 13 4a Compounds 9ab (154 mg 0.447 mmol) and sulfuric acid (0.5 M; 4.5 cm3) were heated at 100 8C for 8 h. After the mixture had cooled to room temperature aq. KHCO3 (10) was added to neutralize it. The aqueous phase was extracted with dichloromethane (3 times; 5 cm3) and the combined organic extract was washed with water (5 cm3) dried over MgSO4 and concentrated under reduced pressure.Flash chromatography of the residue (hexanendash;ethyl acetate 7 3) gave keto alcohol 13 (38 mg 47). Using the same methodology acidic hydrolysis of glycosides 11ab (210 mg 0.61 mmol) for 11 h gave the same keto alcohol 13 (46 mg 42). Similar treatment for each of the two diastereoisomers 11a and 11b allowed us to measure the rotation of enantiomerically pure materials. Isomer 11a gave compound (2)-13 aD 26 29 (c 0.6 CH2Cl2) and isomer 11b gave compound (1)-13 aD 27 19 (c 0.55 CH2Cl2); (1)-13 nmax(neat)/cm21 3446 3019 2932 2858 1684 1518 1441 1215 1122 and 1035; dH(200 MHz; CDCl2) 1.22ndash;1.98 (m 14 H 3- 4- 5- 7- 8- 9- and 10-H2) 2.04ndash;2.30 (br s 1 H OH) 2.68ndash;2.87 (m 2 H 1- and 6-H) and 4.04 (m 1 H 2-H); dC(50 MHz; CDCl3) 21.0 26.0 26.34 26.40 27.60 29.24 and 35.23 (C-3 -4 -5 -7 -8 -9 and -10) 54.69 (C-6) 62.49 (C-1) 69.33 (C-2) and 217.78 (CO).2-(2-Oxobicyclo3.2.2nona-3,8-dien-6-yl)acetaldehyde 15ab A solution of compounds 4ab (400 mg 1.18 mmol) in sulfuric acid (0.5 M; 15 cm3) was heated at 80 8C for 2.5 h. After cooling to room temperature the reaction mixture was neutralized with aq. KHCO3 (10). The aqueous phase was extracted with dichloromethane (2 times; 10 cm3) and the combined organic phase was washed with water (5 cm3) dried over MgSO4 and concentrated. This oil was purified by flash chromatography over silica gel (hexanendash;ethyl acetate 6 4) to give compounds 15ab (57 mg 31) (in a 70 30 ratio) and hemiacetals 16ab (25 mg 13) (in a 25 75 ratio).Compounds 15ab (Found C 73.1; H 7.0. C11H12O2?0.25 H2O requires C 73.1; H 7.0); nmax(neat)/cm21 3020 2930 1736 1710 1677 1668 1520 1422 1215 and 1022. Compound 15a dH(250 MHz; CDCl3) 1.50 (ddd J 4 6 and 14 1 H 14-Hexo) 2.27 (ddd J 1 10 and 14 1 H 14-Hendo) 2.50ndash; 2.59 (m 2 H 16-H2) 2.77ndash;2.90 (m 1 H 15-H) 3.16 (br t 1 H J 8 10-H) 3.48 (m 1 H 13-H) 5.79 (dd J 2 and 11 1 H 8-H) 6.20 (t 1 H 12-H) 6.42 (t 1 H 11-H) 7.12 (dd J 9 and 11 1 H 9-H) and 9.75 (t J 1 1 H CHO); dC(50 MHz; CDCl3) 28.92 (C-14) 33.14 (C-15) 41.53 (C-10) 52.08 (C-13 and -16) 128.35 and 129.86 (C-11 and -12) 135.55 (C-8) 152.87 (C-9) 197.57 (CO) and 200.99 (CHO). Compound 15b dH(250 MHz; CDCl3) 1.38 (ddd J 3 6 and 14 1 H 14-Hendo) 2.44 (ddd J 1 7 and 14 1 H 14-Hexo) 2.50ndash; 2.59 (m 2 H 16-H2) 2.77ndash;2.90 (m 1 H 15-H) 3.31 (br t J 8 1 H 10-H) 3.48 (m 1 H 13-H) 5.90 (dd J 2 and 11 1 H 8-H) 6.05 (t J 8 1 H 12-H) 6.60 (t J 8 1 H 11-H) 6.86 (dd J 9 and 11 1 H 9-H) and 9.80 (t J 1 1 H CHO); dC(50 MHz; CDCl3) 28.04 (C-14) 34.26 (C-15) 41.27 (C-10) 49.86 (C-16) 51.79 (C-13) 125.69 and 131.44 (C-11 and -12) 139.49 (C-8) 149.70 (C-9) 196.64 (CO) and 200.74 (CHO).Compounds 16ab (Found C 67.6; H 7.0. C11H14O3 requires C 68.0; H 7.3); mp 102 8C; nmax(KBr)/cm21 3389 3019 2932 1700 1685 1216 1157 1085 and 1046; m/z 194 (M1 1.7) 176 (M1 2 H2O 7.2) 150 (7) 105 (41) 91 (86) 79 (100) 78 (68) and 65 (12). Compound 16a dH(250 MHz; CDCl3) 1.60 (ddd J 3 13 and 13 1 H 14-H) 1.67 (ddd J 5 9 and 13 1 H 16-H) 1.89 (ddd J 3 5 and 13 1 H 16-H9) 2.26 (ddd J 3 6 and 13 2 H 14-H9 and 15-H) 2.53 (d J 17 1 H 8-H) 2.86ndash;3.02 (m 1 H 10-H) 3.13 (dd J 8 and 17 1 H 8-H9) 3.23 (br t J 6 1 H 13-H) 4.10 (br s 1 H OH) 4.47 (br t J 8 1 H 9-H) 4.86 (dd J 1 and 9 1 H 7-H) 6.17 (dt J 6 and 8 1 H 12-H) and 6.34 (dt J 6 and 8 1 H 11-H); dC(62 MHz; CDCl3) 28.42 (C-15) 32.29 (C-14) 36.61 (C-10) 37.30 (C-16) 46.70 (C-8) 50.84 (C-13) 70.54 (C-9) 87.49 (C-7) 130.94 and 133.33 (C-11 and -12) and 211.75 (CO).Compound 16b dH(200 MHz; CDCl3) 1.51ndash;1.71 (m 1 H 14-H) 1.82ndash;2.12 (m 2 H 16-H2) 2.34ndash;2.42 (m 2 H 14-H9 and 15-H) 2.56 (d J 17 1 H 8-H) 2.86ndash;3.02 (m 1 H 10-H) 3.02 (dd J 9 and 17 1 H 8-H9) 3.23 (br t J 6 1 H 13-H) 3.81 (br s 1 H OH) 4.32 (br t J 8 1 H 9-H) 5.30 (d 1 H 7-H) 6.17 (dt J 6 and 8 1 H 12-H) and 6.34 (dt J 6 and 8 1 H 11-H); dC(62 MHz; CDCl3) 25.07 (C-15) 30.77 (C-14) 34.01 (C-16) 36.79 (C-10) 48.05 (C-8) 51.04 (C-13) 66.69 (C-9) 90.70 (C-7) 131.45 and 133.53 (C-11 and -12) and 210.21 (CO).Acknowledgements We thank C.N.R.S. and Universiteacute; Paris-Sud for financial support. 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Augeacute; and N. Lubin J. Chem. Soc. Perkin Trans. 1 1990 3011; (b) A. Lubineau and Y. Queneau J. Org. Chem. 1987 52 1001. 8 A. Lubineau and Y. Queneau Tetrahedron Lett. 1985 26 2653. For relevent studies on asymmetric Dielsndash;Alder reactions using chiral diene derivatives from carbohydrates see R. C. Gupta P. A. Harland and R. J. Stoodley J. Chem. Soc. Chem. Commun. 1983 754; A. Lubineau J. Augeacute; H. Bienaymeacute; N. Lubin and Y. Queneau Cycloaddition Reactions in Carbohydrate Chemistry ed.R. M. Giuliano ASC Symposium Series 1992 vol. 494 p. 147. 9 D. C. Rideout and R. Breslow J. Am. Chem. Soc. 1980 102 7816; P. A. Grieco P. Garner and Z. M. He Tetrahedron Lett. 1983 24 1897; A. Lubineau J. Augeacute; and Y. Queneau Synthesis 1994 741. 10 A. Lubineau J. Augeacute; H. Bienaymeacute; Y. Queneau and M. C. Scherrmann Carbohydrates as Organic Raw Materials II ed. G. Descotes VCH Weinheim Germany 1993 p. 99; A. Lubineau H. Bienaymeacute; Y. Queneau and M. C. Scherrmann New J. Chem. 1994 18 279. Paper 7/02447I Received 10th April 1997 Accepted 2nd June 1997